Cyclophosphamide and Anti-thymocyte Globulin Followed By Methotrexate and Cyclosporine in Preventing Chronic Graft-Versus-Host Disease in Patients With Severe Aplastic Anemia Undergoing Donor Bone Marrow Transplant

NCT ID: NCT00343785

Last Updated: 2017-04-13

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

21 participants

Study Classification

INTERVENTIONAL

Study Start Date

2006-02-28

Study Completion Date

2012-08-31

Brief Summary

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This clinical trial is studying how well giving cyclophosphamide together with anti-thymocyte globulin followed by methotrexate and cyclosporine works in preventing chronic graft-vs-host disease (GVHD) in patients with severe aplastic anemia undergoing donor bone marrow transplant. Giving low doses of chemotherapy, such as cyclophosphamide, before a donor bone marrow transplant helps stop the growth of abnormal cells. It also stops the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune system and help destroy any remaining abnormal cells. Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving anti-thymocyte globulin before and methotrexate and cyclosporine after transplant may stop this from happening

Detailed Description

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PRIMARY OBJECTIVES:

I. Minimize the incidence of chronic GVHD by restricting the transplanted marrow dose to 2.0-2.5 x 10\^8 nucleated cells/kg.

SECONDARY OBJECTIVES:

I. Engraftment and overall survival.

OUTLINE:

CONDITIONING REGIMEN: Patients receive cyclophosphamide intravenously (IV) on days -5 to -2 and anti-thymocyte globulin IV over 4-10 hours on days -4 to -2.

TRANSPLANTATION: Patients undergo allogeneic bone marrow transplantation on day 0.

GVHD PROPHYLAXIS: Patients receive methotrexate IV on days 1, 3, 6, and 11 and cyclosporine IV over 1 hour or orally (PO) twice daily on days -1 to 50, followed by a taper until 6 months after grafting.

After completion of study treatment, patients are followed up at on day 180, 1 year, 1.5 years, 2 years, 3 years, and yearly thereafter.

Conditions

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Aplastic Anemia

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Treatment (conditioning regimen, transplant, GVHD prophylaxis)

Patients receive a conditioning regimen comprising cyclophosphamide IV on days -5 to -2 and anti-thymocyte globulin IV over 4-10 hours on days -4 to -2. Patients undergo allogeneic bone marrow transplantation on day 0. Patients then receive GVHD prophylaxis comprising methotrexate IV on days 1, 3, 6, and 11 and cyclosporine IV over 1 hour or PO twice daily on days -1 to 50, followed by a taper until 6 months after grafting.

Group Type EXPERIMENTAL

cyclophosphamide

Intervention Type DRUG

Given IV

anti-thymocyte globulin

Intervention Type BIOLOGICAL

Given IV

cyclosporine

Intervention Type DRUG

Given IV or PO

allogeneic bone marrow transplantation

Intervention Type PROCEDURE

Undergo allogeneic bone marrow transplantation

methotrexate

Intervention Type DRUG

Given IV

DNA analysis

Intervention Type GENETIC

Correlative studies

flow cytometry

Intervention Type OTHER

Correlative studies

polymorphism analysis

Intervention Type GENETIC

Correlative studies

laboratory biomarker analysis

Intervention Type OTHER

Correlative studies

Interventions

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cyclophosphamide

Given IV

Intervention Type DRUG

anti-thymocyte globulin

Given IV

Intervention Type BIOLOGICAL

cyclosporine

Given IV or PO

Intervention Type DRUG

allogeneic bone marrow transplantation

Undergo allogeneic bone marrow transplantation

Intervention Type PROCEDURE

methotrexate

Given IV

Intervention Type DRUG

DNA analysis

Correlative studies

Intervention Type GENETIC

flow cytometry

Correlative studies

Intervention Type OTHER

polymorphism analysis

Correlative studies

Intervention Type GENETIC

laboratory biomarker analysis

Correlative studies

Intervention Type OTHER

Other Intervention Names

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CPM CTX Cytoxan Endoxan Endoxana ATG ATGAM lymphocyte immune globulin Thymoglobulin ciclosporin cyclosporin cyclosporin A CYSP Sandimmune bone marrow therapy, allogeneic bone marrow therapy, allogenic transplantation, allogeneic bone marrow transplantation, allogenic bone marrow amethopterin Folex methylaminopterin Mexate MTX

Eligibility Criteria

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Inclusion Criteria

* Any patient who has aplastic anemia with marrow failure involving 2 of the three following criteria: granulocytes \< 500/uL; a corrected reticulocyte count of \< 1%; platelet count of \< 20,000/uL
* Availability of an human leukocyte antigen (HLA)-matched family member
* DONOR: Family member who is HLA-matched
* DONOR: If more than one HLA-matched family member is available, priority will be given to a donor who is genotypically HLA-identical, of appropriate cytomegalovirus (CMV) serology, ABO compatible, and, in case of a female donor, non-parous

Exclusion Criteria

* Severe disease other than aplastic anemia that would severely limit the probability of survival during the graft procedure:

* Patients who have developed clonal cytogenetic abnormalities or myelodysplastic syndrome (preleukemia)
* Patients with Fanconi's anemia
* Aplasia secondary to radiation or cytotoxic chemotherapy
* Patients with paroxysmal nocturnal hemoglobinuria who have not developed aplastic anemia
* Severe organ toxicities:

* Cardiac insufficiency requiring treatment or symptomatic coronary artery disease;
* Severe hypoxemia , partial pressure of oxygen (pO2) \< 70 mm Hg, with decreased diffusion capacity of carbon monoxide (DLCO) \< 70% of predicted; or mild hypoxemia, pO2 \< 80 mm Hg with severely decreased DLCO \< 60% of predicted;
* Impaired renal function (creatinine \> 2 times upper limit of normal or estimated creatinine clearance \< 60 ml/min)
* Fungal infections with radiological progression after receipt of amphotericin B or active triazole for greater than 1 month
* Human immunodeficiency virus (HIV)-positive patients
* Females who are pregnant or breast-feeding
* DONOR: Donors who have increase anesthetic risk and are not able psychologically and medically to tolerate the procedure
* DONOR: HIV-positive donors
Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role collaborator

Fred Hutchinson Cancer Center

OTHER

Sponsor Role lead

Responsible Party

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Rainer Storb

Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Rainer Storb

Role: PRINCIPAL_INVESTIGATOR

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Locations

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Huntsman Cancer Institute/University of Utah

Salt Lake City, Utah, United States

Site Status

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Seattle, Washington, United States

Site Status

Froedtert and the Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Site Status

Countries

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United States

Other Identifiers

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NCI-2010-01781

Identifier Type: REGISTRY

Identifier Source: secondary_id

P01HL036444

Identifier Type: NIH

Identifier Source: secondary_id

View Link

2054.00

Identifier Type: -

Identifier Source: org_study_id

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